Survival
Includes all samples, unadjusted. We performed a landmark analysis
and also analyzed this same data with peto-peto instead of standard
log-rank. Both were still significant, therefore an FDR correction would
not change our findings here.
Cox model (No interaction)
Supplemntal figure XX. Forest plot for adjusted Cox
model. Cox proportional hazards regression to estimated
efficacy of vitamin C on overall survival was adjusted for patient age
at inclusion, gender, hemoglobin levels at inclusion, and whether or not
they had been diagnosed with CCUS.

Cox model (Age interaction)
Supplemental figure XX. Forest plot for adjusted Cox model in
age interaction. Cox proportional hazards regression to
estimated efficacy of vitamin C as a function of age. Age was mean
centered and converted to decades to improve hazard ratio scales.
Overall vitamin C was still effective, with evidence that it’s efficacy
decreases with age.

2-year Landmark
Maybe Figure? A 2 year landmark analysis was
performed to determine if there was still evidence of vitamin C efficacy
but removing individuals who had events prior to 2 years. This landmark
analysis ensures the effects of vitamin C had sufficient time to reach
efficacy.

Subgroups (suppl)
All subgroup analyses include only the hazard ratio with 95% CI as
these are exploratory.
TET1 or IDH1/2 at baseline
Supplemental Figure XX. Overall survival by TET2 or IDH1/2
mutation status. Hazard ratio and confidence intervals were
estimated using Cox proportional hazards models on data stratified by
TET2 and IDH1/2 mutation status. Survival curves and estimates are
consistent with the primary outcome.

Inclusion Vitamin C Group
Supplemental figure XX. Overall survival by vitamin C
adequacy at inclusion. Hazard ratio and confidence intervals
were estimated using Cox proportional hazards models on data stratified
by patients with vitamin C deficiency, inadequacy, or adequacy at
inclusion. Results are consistent with the primary outcome, however
there is some evidence that vitamin C supplementation in those with
adequate vitamin C levels at inclusion may be less effective than
supplementation in individuals with less than adequate plasma vitamin
C.

Diagnostic subgroup
Supplemental figure XX. Overall survival by diagnostic
subgroup at inclusion. Hazard ratio and confidence intervals
were estimated using Cox proportional hazards models on data stratified
by diagnosis at inclusion. CCUS appears to be a subgroup that can
benefit particularly well from vitamin C supplementation.

Competing risk regression (progression)
For this analysis death is a competing risk of high-risk progression.
We are a bit limited in sample size and events; there are only 14
progression events. Power to detect any differences in progression is
quite low and we will have difficulty adjusting for any covariates here.
We see corroboration with out overall survival findings that death (the
dotted lines) are significantly different, however we do not have enough
evidence to determine if progression also differs (p = 0.22).
##
## Variable Coef SE HR 95% CI p-value
## VitaminC -0.680 0.557 0.51 0.17, 1.51 0.22

Global Methylation
Figure XX. Global methylation changes over time by treatment
arm A) 5mC/dG and B) 5hmC/5mC levels for each patient at
inclusion and end-of-therapy (EOT) and the change in these measures
between inclusion and EOT. Data were analyzed using robust linear
mixed-effects models with a random intercept for each patient and an
interaction between treatment and timepoint to assess if measures
changed differently over time. Models also included a covariate for
batch.
